Beyond phrenology: brain and language in the next millennium.
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Brain↗
Biomedical subjects
F Dick
Publications and source records attributed to F Dick.
Neurological deficits in solvent-exposed painters: a syndrome including impaired colour vision, cognitive defects, tremor and loss of vibration sensation.
Five individuals are described who had participated in a study of former dockyard painters. All had worked between 16 years and 45 years as industrial painters, much of the time inside ships. All underwent structured neurological examination, colour vision testing (allowing calculation of a colour confusion index corrected for age and alcohol), and detailed psychometric testing. An occupational history sufficient to allow estimation of past exposure to solvents was taken. All gave a history of exposure to high concentrations of solvents at work, and several described episodes of acute narcosis. All showed neurological deficits and some had overt neurological disease, although in no case had this previously been linked to their work. The most striking features, sufficient to constitute a syndrome, were acquired blue-yellow colour vision deficits, coarse tremor, impaired vibration sensation in the legs and cognitive impairment. Their estimated cumulative exposures to solvents ranged between the equivalent of 13 and 37 calendar years working at the Occupational Exposure Standard concentration (OES years). This study for the first time gives an indication of the concentrations of solvents likely to lead to serious neurological disease in humans. It serves as a reminder to physicians to take an occupational history from patients with obscure neurological or psychological impairment.
Aged↗
Impairment of colour vision in workers exposed to organic solvents.
OBJECTIVES: To investigate loss of colour vision related to exposure to solvents and the role of three enzyme polymorphisms in modifying the risk in exposed workers. METHODS: A sample was studied of 68 male dockyard workers and 42 male community controls with and without neuropsychological symptoms from a previous cross sectional study. Indices of cumulative and intensity based exposure to solvents were calculated for all subjects. Alcohol, drug, and smoking histories were obtained. Colour vision was tested by Lanthony D15d colour vision test. Genotype of glutathione S-transferase M1 and T1 and N-acetyltransferase 2 polymorphisms were determined. RESULTS: The relation between impairment of colour vision and exposure to solvents was investigated with multiple regression techniques. Increasing annual exposure to solvents was significantly associated with reduced colour vision (p=0.029). Impairment of colour vision was not associated with neuropsychological symptoms as measured by the Q16 solvent symptom questionnaire. No significant association was found between acquired impairment of colour vision and genetic polymorphisms when GSTM1, GSTT1 or NAT2 phenotypes were included in the analyses. CONCLUSIONS: Exposure to mixed solvents is associated with impairment in colour vision, the risk increases with increasing exposure. The risk of impairment of colour vision was not altered in this study by the presence of different GSTM1, GSTT1 or NAT2 polymorphisms.
Arylamine N-Acetyltransferase↗
Medical complications after stroke: a multicenter study.
BACKGROUND AND PURPOSE: This prospective, multicenter study was performed to determine the frequency of symptomatic complications up to 30 months after stroke using prespecified definitions of complications. METHODS: We recruited 311 consecutive stroke patients admitted to hospital. Research nurses reviewed their progress on a weekly basis until hospital discharge and again at 6, 18, and 30 months after stroke. RESULTS: Complications during hospital admission were recorded in 265 (85%) of stroke patients. Specific complications were as follows: neurological-recurrent stroke (9% of patients), epileptic seizure (3%); infections-urinary tract infection (24%), chest infection (22%), others (19%); mobility related-falls (25%), falls with serious injury (5%), pressure sores (21%); thromboembolism-deep venous thrombosis (2%), pulmonary embolism (1%); pain-shoulder pain (9%), other pain (34%); and psychological-depression (16%), anxiety (14%), emotionalism (12%), and confusion (56%). During follow-up, infections, falls, "blackouts, " pain, and symptoms of depression and anxiety remained common. Complications were observed across all 3 hospital sites, and their frequency was related to patient dependency and duration after stroke. CONCLUSIONS: Our prospective cohort study has confirmed that poststroke complications, particularly infections and falls, are common. However, we have also identified complications relating to pain and cognitive or affective symptoms that are potentially preventable and may previously have been underestimated.
Accidental Falls↗
Smoking and risk of non-Hodgkin lymphoma subtypes in a cohort of older women.
Although non-Hodgkin lymphoma (NHL) has not been considered to be a smoking-related malignancy, recent investigations suggest otherwise. We evaluated this association in a cohort of 37,336 women, aged 55-69 years, who reported in a mailed questionnaire in 1986 information regarding smoking history as well as demographic, medical history and dietary factors. Cancer and mortality experience through 1996 was determined by linkage to the Iowa Cancer Registry and other databases; there were 200 incident cases of NHL during the 380,231 total person-years of follow-up. Compared to never smokers, former (age-adjusted RR = 1.0; 95% CI 0.8-1.5) and current smokers (age-adjusted RR = 1.0; 95% CI 0.7-1.5) were not at elevated risk of NHL, and there was no trend with pack-years smoked (Ptrend = 0.3). Multivariate adjustment for other NHL risk factors did not alter these findings. Age-adjusted analysis by NHL subtype revealed a suggestive positive association of smoking with follicular NHL [(RRformer = 1.3; 95% CI 0.6-2.8), (RRcurrent = 1.8; 95% CI 0.8-3.8)], which strengthened after multivariate adjustment [(RRformer = 1.6; 95% CI 0.7-3.4), (RRcurrent = 2.3; 95% CI 1.0-5.0)]; there was no association for diffuse or small cleaved-cell NHL. Our study findings, which are consistent with other recent investigations, suggest that smoking may be associated with an increased risk of follicular NHL.
Age Factors↗
Health effects of solvent exposure among dockyard painters: mortality and neuropsychological symptoms.
OBJECTIVES: To study mortality and prevalence of neuropsychological symptoms among a cohort of painters known to have been heavily exposed to organic solvents. METHODS: A mortality study of 1292 male painters who had worked in a dockyard in Scotland for > or = 1 year between 1950 and 1992 comprised a nested cross sectional study of 953 surviving painters from the cohort and 953 male non-painters randomly selected from the local population and a case-control study of those with high symptom scores. Mortality, symptoms, and risks associated with painting, adjusting for age, education, smoking, alcohol, and personality were measured. RESULTS: The proportional mortality ratio for all cancers was not increased significantly (110 (95% confidence interval (95% CI) 84 to 143), except for a possible excess of deaths from ischaemic heart disease (132, 105 to 164). Standardised mortality ratios were not significantly increased. Among the 260 surviving painters and 539 community controls who responded to the questionnaire there was a significant excess of symptoms among painters; adjusted relative risk (RR) increased significantly with increasing symptom score. These RRs suggested an exposure-response relation; for a high score (12-22) for all symptoms RR was 2.27 (1.20 to 4.30) for 1-4 years of exposure, 2.42 (1.18 to 4.95) for 5-9 years, 2.89 (1.42 to 5.88) for 10-14 years, and 3.41 (1.82 to 6.36) for 15-41 years, compared with controls. In multivariate analyses, painting exposure, and aging were associated with high symptom scores and there was again an increased risk relative to time worked as a painter. CONCLUSION: This study supports the hypothesis that heavy and prolonged exposure to paint solvents leads to neuropsychological ill health.
Adult↗
Core morphological concepts of disease for second-year medical students.
With the increasing emphasis on independent learning and early patient contact, the time in the undergraduate medical curriculum for formal teaching of morphology of disease is decreasing. Thus, we thought it advisable to identify those core morphological entities of disease that should not get lost in the new paradigm. Our approach was to list all disease processes in Robbins Pathologic Basis of Diseases, 5th edition, that have distinguishing gross or microscopic characteristics. Appropriate portions of this list of 952 morphological entities from the Robbins textbook were distributed to 46 clinical specialists and pathology faculty. Each of these was asked to strongly agree, agree, disagree, or strongly disagree with the following for each entry on the list: "For purposes of developing concepts of disease, an M2 physician in training should recognize classical examples or a diagrammatic representation of the following lesions, and distinguish them from each other." Responses resulted in a consensus core list of 63 general disease process lesions and 545 organ system lesions, for a total of 608. These 608 core morphological entities were incorporated into our course by means of (1) a computer program with over 1,022 images and clinical-pathological correlations, and (2) a core list of morphological objectives for each unit in the course. In general, entities were judged noncore material if they were rare or were microscopic lesions of primary interest to pathologists and provided no major pathomorphologic concepts. The computer program as a supplement to glass slides and gross specimens has been very well accepted by students, and satisfactory performance on examinations has been maintained in spite of a 25% reduction in pathology course contact hours.
Clinical Medicine↗
Analysis of T cell receptor-gamma gene rearrangements by denaturing gradient gel electrophoresis of GC-clamped polymerase chain reaction products. Correlation with tumor-specific sequences.
We describe a modified denaturing gradient gel electrophoresis (DGGE) procedure with a 40-nucleotide GC clamp in the polymerase chain reaction to improve resolution in amplifying T cell receptor-gamma (TCR-gamma) rearrangements. DNA from 46 cases of lymphoblastic leukemia/lymphoma, 5T cell lines, 2 B cell lines, 7 normal lymphocytes, and 3 cases of Hodgkin's disease was amplified by polymerase chain reaction. In addition, 20 cases of paraffin-embedded T cell lymphomas and 5 cases of reactive hyperplasia were also studied. Clonal TCR-gamma rearrangements were identified on DGGE by the presence of a predominant band. Results obtained from 5 T cell lines and 12 lymphoblastic leukemia/lymphomas containing known TCR-gamma gene rearrangements revealed 100% concordance in detecting clonal rearrangements between DGGE and traditional Southern blot analysis. Of the remaining 34 lymphoblastic leukemia/lymphoma cases studied by DGGE alone, 30 were positive. DGGE analysis of 10 lymphoblastic leukemia/lymphoma cases with known group IV gamma to J gamma 1 or J gamma 2 rearrangement sequences confirmed that the electrophoretic migration was dependent on the tumor-specific rearranged TCR-gamma sequence. In addition, 17 of 20 cases of paraffin-embedded T cell lymphomas were positive by DGGE, 6 of which had the clonal population also identified in fresh tissue DNA. DGGE analysis of GC-clamped polymerase chain reaction products can provide a way to more accurately detect TCR-gamma clonality of lymphoid tumors and can be applied to archival tissues.
Base Sequence↗
Acid cleavage/deprotection in Fmoc/tBu solid-phase peptide synthesis.
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Acids↗
Paranuclear blue inclusions in metastatic undifferentiated small cell carcinoma in the bone marrow.
Paranuclear blue inclusions (PBIs) are frequently identified within metastatic undifferentiated small cell carcinoma (SCC) cells on air-dried bone marrow aspirates stained with Wright's stain. To determine the sensitivity and specificity of this finding, 116 bone marrow aspirates containing metastatic neoplasms were evaluated for the presence and frequency of PBIs. Bone marrow specimens included 47 cases of metastatic SCC of the lung, 13 cases of large cell lymphoma, 19 cases of neuroblastoma, five cases of small, noncleaved cell lymphoma, seven cases of rhabdomyosarcoma, three cases of Ewing's sarcoma, three cases of other sarcomas, and 19 cases of non-small cell carcinoma (adenocarcinoma). PBIs were identified in 40 of 47 (85%) cases of SCC and their frequency varied from 0 to 24% of tumor cells among different cases. In approximately half the cases of SCC, PBIs were identified in 1 to 4% tumor cells; and in eight cases, PBIs were present in 5% or more of tumor cells. PBIs were also identified in two of seven (29%) cases of rhabdomyosarcoma and one case of malignant peripheral nerve sheath tumor, but they were not seen in Ewing's sarcoma, small non-cleaved cell lymphoma, large cell lymphoma, neuroblastoma, or non-small cell carcinoma. In addition, PBIs were not seen in alcohol-fixed, Papanicolaou-stained cytology specimens containing SCC. Ultrastructurally, PBIs may represent phagocytized nuclear/cellular material. PBIs are a feature of small cell carcinoma on air-dried, cytologic material stained with Romanowsky type stains. Their presence may provide diagnostic information with regard to the differential diagnosis of metastatic SCC in the bone marrow. Future studies evaluating non-bone marrow Wright's stained fine-needle aspiration specimens are needed to determine if PBIs are useful in distinguishing SCC from other poorly differentiated tumors in the cytology laboratory.
Bone Marrow↗
Familial cancers associated with subtypes of leukemia and non-Hodgkin's lymphoma.
To investigate whether a history of hematolymphoproliferative cancers (HLP) and other cancers among a parent or sibling is a risk factor for specific subtypes of leukemia and non-Hodgkin's lymphoma (NHL), data from a population-based case-control study, in Iowa and Minnesota, of 578 leukemia cases, 622 NHL cases and 1245 controls were evaluated. Having at least one sibling with HLP significantly increased the risk for all leukemias combined (odds ratio (OR) = 2.3) and for NHL (OR = 2.7). In particular, chronic lymphocytic leukemia (CLL) was significantly increased among those reporting a sibling with leukemia (OR = 3.0) or lymphoma (OR = 4.3). Elevated risks of small lymphocytic NHL (SML) (OR = 7.3) and diffuse NHL (DIF) (OR = 5.4) were also observed among subjects who had a sibling with lymphoma (primarily Hodgkin's disease). A significantly increased risk of follicular NHL was noted among those with a sibling history of pancreatic cancer (OR = 4.8) and colorectal cancer (OR = 2.7). Parental history of HLP was not associated with any type of leukemia or NHL. A history of stomach cancer among parents was associated with a 2-fold elevation of CLL and DIF compared to controls. Increased risks of CLL and DIF were also linked to breast cancer among sisters and mothers, respectively. Prostate cancer among fathers increased the risk 2-fold for CLL and 3-fold for SML. This study confirms some familial cancer associations previously reported for leukemia and NHL, and provides new information regarding the various subtypes of leukemia and NHL.
Adult↗
Pesticide exposures and other agricultural risk factors for leukemia among men in Iowa and Minnesota.
Mortality surveys and death certificate studies have suggested an association between leukemia and farming. To investigate whether exposure to carcinogens in an agricultural setting is related to risk of leukemia, the authors conducted a population-based case-control interview study of 578 white men with leukemia and 1245 controls living in Iowa and Minnesota. Consistent with recent mortality studies, there were slight, but significant, elevations in risk for all leukemia [odds ratio (OR) 1.2] and chronic lymphocytic leukemia (OR 1.4) for farmers compared to nonfarmers. There were no significant associations with leukemia for exposure to specific fungicides, herbicides (including 2,4-D and 2,4,5-T), or crop insecticides. However, significantly elevated risks for leukemia of greater than or equal to 2.0 were seen for exposure to specific animal insecticides including the organophosphates crotoxyphos (OR 11.1), dichlorvos (OR 2.0), and famphur (OR 2.2) and the natural product pyrethrins (OR 3.7) and the chlorinated hydrocarbon methoxychlor (OR 2.2). There were also smaller, but significant, risks associated with exposure to nicotine (OR 1.6) and DDT (OR 1.3). This finding of elevated risks for insecticides used on animals deserves further evaluation.
Agricultural Workers' Diseases↗
Use of the working formulation for non-Hodgkin's lymphoma in epidemiologic studies: agreement between reported diagnoses and a panel of experienced pathologists.
Independent review of slides of 668 cases of non-Hodgkin's lymphoma (NHL) by a panel of 4 experienced pathologists using the Working Formulation (WF) allowed determination of the agreement between reported diagnoses and panel review of slides. The panel agreed with the reported diagnosis of NHL in 93% of cases, but with the NHL subtype in only 55% of cases overall. The ability of the panelists to agree among themselves, however, was only slightly better than the panelists' agreement with the reported diagnosis (60% vs. 54%, respectively). Agreement of the panel with the reported subtype diagnosis varied from 14% to over 90%. The best agreement was with small lymphocytic lymphoma and follicular subtypes. Conclusions from this study are: 1) The WF functions well as common language for translation and comparison of diagnoses of subtypes of NHL. 2) Relative to time and cost involved, panel review using only light microscopy may not be useful in epidemiologic studies of NHL. 3) Small lymphocytic and follicular subtypes of NHL can be used more confidently in epidemiologic studies than can other subtypes whether the subtyping is done from abstracted reports or by panel review.
Humans↗
Postleukemic dysmyelopoiesis.
The morphologic and clinical features of four patients who developed significant bone marrow and blood dyspoiesis after successful chemotherapy for acute nonlymphocytic leukemia (ANLL) are described. This postleukemic dyspoiesis developed 1-6 months after leukemia induction therapy and persisted for 5-20 months in a relatively stable state. This period of prolonged dyspoiesis was not associated with rising myeloblast counts or clinical evidence of relapse. Dyspoietic abnormalities developed while two patients were receiving maintenance chemotherapy; the other two patients received no maintenance therapy. The dyspoietic changes in these four patients greatly exceeded those noted in a control group of ANLL patients on maintenance chemotherapy. The morphologic features of postleukemic dysmyelopoiesis were similar to those described in preleukemic dysmyelopoietic disorders. Erythroid abnormalities included hyperplasia with ring sideroblasts, megaloblastic changes, and cytoplasmic PAS reactivity. Myeloid abnormalities consisted of left-shifted granulopoiesis with hyper- and hyposegmentation; megakaryocytic abnormalities included hyperplasia with a predominance of hypolobulated forms. Three of the four patients eventually suffered relapse and have died. The fourth patient died of sepsis after 20 months of pancytopenia and dysmyelopoiesis. Theories to explain the development of postleukemic dysmyelopoiesis are presented which emphasize the possibility of drug-induced leukemia cell differentiation. Cytogenetic studies will be necessary to establish any relationship between ANLL and the subsequent postleukemic dysmyelopoiesis.
Acute Disease↗
Lack of labelling of microglial cells following microinjection of [3H] beta-alanine: an electron microscopic autoradiographic study.
Following axotomy of the facial nerve, the uptake of [3H] beta-alanine into different types of glial cells in the facial nucleus was studied by autoradiography. A marked proliferation of microglial cells, predominantly in a satellite position to neurons, was accompanied by a localization of [3H] beta--alanine over astrocytes and oligodendrocytes but not over microglial cells. Microglial cells therefore appear to be a functionally distinct cell type and should not be classified with the macroglia.
Alanine↗
Immunoblastic lymphadenopathy with pulmonary infiltrates, hypocomplementemia and vasculitis. A hyperimmune syndrome.
A detailed description of the clinical and morphologic characteristics of four patients with immunoblastic lymphadenopathy, pulmonary infiltrates, hypocomplementemia and vasculitis is presented. Noteworthy in the patients described here is the clinical similarity to patients with collagen-vascular diseases and systemic drug reactions. The frequent occurrence of pulmonary symptoms, bilateral interstitial infiltrates and pleural effusions is emphasized. The morphology suggests stimulation of the immune system by antigenic agents, and the low complement levels and the presence of vasculitis suggest that circulating immune complexes may be present. Immunoblastic lymphadenopathy may represent a syndrome in which the adenopathy is but a nonspecific part of a systemic hyperimmune response to unknown antigens. The clinical course of the patients reviewed suggests that supportive treatment and corticosteroids constitute the safest therapeutic approach.
Adult↗
Secific in vivo autoradiographic localization of [3H]-beta-alanine uptake sites in macro-as opposed to microglial cells [proceedings].
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Alanine↗
Differential labeling of glial cells and GABA-inhibitory interneurons and nerve terminals following the microinjection of (beta-3H)alanine, (3H)DABA and (3H)GABA into single folia of the cerebellum.
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Alanine↗